5-Hydroxytryptamine 1A receptor (IPR000610)
Short name: 5HT1A_rcpt
Overlapping homologous superfamilies
5-hydroxytryptamine (5-HT) or serotonin, is a neurotransmitter that it is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS). It is implicated in a vast array of physiological and pathophysiological pathways. Receptors for 5-HT mediate both excitatory and inhibitory neurotransmission, and modulate the release of many neurotransmitters including glutamate, GABA, dopamine, epinephrine/norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin and cortisol. In the CNS, 5-HT receptors can influence various neurological processes, such as aggression, anxiety and appetite and, as a, result are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics and anorectics [PMID: 18476671].
The 5-HT receptors are grouped into a number of distinct subtypes, classified according to their antagonist susceptibilities and their affinities for 5-HT. With the exception of the 5-HT3 receptor, which is a ligand-gated ion channel [PMID: 11989819], all 5-HT receptors are members of the rhodopsin-like G protein-coupled receptor family [PMID: 18476671], and they activate an intracellular second messenger cascade to produce their responses.
The 5-HT1 receptors are a subfamily of 5-HT receptors that were originally classified according to their inhibition of adenylyl cyclase, degree of sequence similarity and their overlapping pharmacological specificities. The subfamily is comprised of five different receptors 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, and they can couple to Gi/Go and mediate inhibitory neurotransmission, although signalling via other transduction systems are known. One of the 5-HT1 receptors, the 5-HT1E receptor, is yet to achieve receptor status from the International Union of Basic and Clinical Pharmacology (IUPHAR), since a robust response mediated via the protein has not been reported in the literature.
5-HT1A receptors are the most widespread of all the 5-HT receptors. They are found pre- and post-synaptically [PMID: 8430834, PMID: 12480158, PMID: 8841890, PMID: 7796165]: in the raphe nuclei they are somatodendritic and act as autoreceptors to inhibit cell firing; whereas postsynaptic 5-HT1A receptors are present in a number of limbic structures, particularly the hippocampus [PMID: 2156831, PMID: 7796165, PMID: 1531498]. 5-HT1A receptors are involved in many neuromodulative processes, and are potential anxiolytic and hypertensive targets [PMID: 8416603, PMID: 9724773, PMID: 9844013, PMID: 15574737]. Receptor antagonists like buspirone [PMID: 2649317] and flesinoxan [PMID: 9169298] have been shown to relieve anxiety [PMID: 9724773, PMID: 1796057] and depression [PMID: 2883013, PMID: 12404310]. Other 5-HT1A receptor agonists decrease blood pressure and heart rate via a central mechanism, by inducing peripheral vasodilation [PMID: 1819150]. This also increases heat dissipation from the organism, causing a decrease in body temperature [PMID: 16455061, PMID: 17702902]. 5-HT1A receptors have been implicated in the neuroendocrine regulation of adrenocorticotrophic hormone (ACTH) [PMID: 15743927]. In the CNS, 5-HT1A receptors exist in the cerebral cortex, hippocampus, septum, amygdala, and in the raphe nucleus in high densities, whilst lower amounts also exist in the basal ganglia and thalamus [PMID: 9935065, PMID: 18761712].
GO:0004993 G-protein coupled serotonin receptor activity
GO:0005887 integral component of plasma membrane